This is the first renewal application for the Chemistry-Biology Interface predoctoral training grant at UC Berkeley. The program provides graduate PhD students with a unique depth of training in the application of chemical principles and techniques to the investigation and modulation of biological systems. The program's goal is to encourage further integration of the fields of chemistry and biology and prepare students for a future of research at this interface. The graduate program provides: 1.) three 10-week rotations for first year students 2.) A core of didactic courses with additional courses selected based on individual student interest, 3.) seminars, 4.) annual retreat, 5.) Poster sessions at the end of each rotation period, 6.) career day, 7.) supergroup meetings, 8.) a PhD dissertation at the chemical biology interface, and 9.) aggressive diversity recruitment efforts. The program selects students from the matriculating pools of first year students in the 4 departments of Chemistry, Molecular and Cell Biology, Chemical engineering, and Bioengineering. Students are selected on the basis of their stated interest in chemical biology research, undergraduate scholastic performance, scores on GRE tests, recommendations from faculty at their undergraduate institutions, and previous research experience. The program has thrived during the first five years with 53 current students, 36 participating faculty, and 12 PhD alumni. Each year the pool of qualified applicants grows larger. The program is positioned to expand to keep up with demand. Annual support for 12 first-year students during their rotation period is requested. RELEVANCE (See instructions): This proposal trains students to develop competence in the fields of chemistry and biology. Students learn the language and techniques to manipulate biological systems at the molecular level, which is key for the design of rational means of diagnosis and treatment of pathological processes. Reciprocally, study of biological problems leads to the development of new synthetic and mechanistic tools in the chemical